Project Summary The thalamus is a relay station for all sensory pathways (except olfactory) to the cerebral cortex. It also regulates sleep and consciousness, supports motor and language function and memory. Its role in cognition is also now increasingly recognized. Given that it serves as a junction for ascending and descending cortical projections, it is likely that thalamus may bear a significant burden of traumatic brain injury (TBI) irrespective of the precise location of physical injury sustained. Thalamic injury may therefore underlie various persisting post-concussive symptoms and cognitive impairment. Recently, our group has provided multiple lines of evidence including altered metabolism, altered tissue microstructure and altered functional communication between various sub-thalamic regions and cortical regions associated with sensory processing after TBI. Our results suggest that the structural and functional integrity of the thalamus may serve as an important factor in the diagnosis and long-term follow-up of TBI patients. These studies have examined the thalamus as a single structure, not as a composite of the various nuclei that reside within it. Recent research has provided evidence that thalamic function is highly selective with individual nuclei performing discrete functions. However, pinpointing injury to specific thalamic nuclei is challenging due to the lack of image contrast within the thalamus. We therefore propose to develop novel MR imaging and multi-modal feature classification methods to segment the thalamus into its individual nuclei and test the hypothesis that post traumatic alterations in the structural and functional integrity of the thalamic nuclei will be associated with progression of specific neuropsychological and cognitive symptoms after mild TBI. We will test this hypothesis through the following aims: (a) Develop and optimize technique to generate a series of T1-based synthetic MPRAGE (SynMPRAGE) images for direct visualization of sub-thalamic nuclei, (b) examine longitudinal structural alterations of the thalamus, and its connectivity on 100 mTBI patients in comparison with orthopedically injured control subjects, and (c) examine longitudinal changes in resting state thalamic connectivity following mTBI. Through the development of novel imaging methodology to directly identify thalamic nuclei and through development and application of improved segmentation techniques using multi-modal classification methods, we plan to understand the pathophysiology of the thalamus and predictive value of MRI measures of thalamic injury in the development of neuropsychological and cognitive deficits in mTBI patients.